Sodium Methoxide → HCID 118086202, compound

HRID 1051599Notes

Reaction equation

HRID 1051599 reaction equation
[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30](F)[N:29]=4)[C:12]([C:16]4[CH:17]=[N:18][N:19]([CH:21]5[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]5)[CH:20]=4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:35])=[O:5])[CH2:3][CH2:2]1.[CH3:36][O-:37].[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([O:37][CH3:36])[N:29]=4)[C:12]([C:16]4[CH:17]=[N:18][N:19]([CH:21]5[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]5)[CH:20]=4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:35])=[O:5])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 118075473HCID 118075473, compound

Product 1

HCID 118086202HCID 118086202, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-cyclopropyl(5-(6-fluoropyridin-2-yloxy)-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.024 g, 0.05 mmol), and sodium methoxide (0.015 g, 0.28 mmol) in N,N-dimethylformamide (1 mL) stirred overnight at 80° C. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (15 mL), washed with brine (2×5 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by preparative-HPLC with the following conditions (Waters I): Column, SunFire Prep C18, 5 um, 19×100 mm; mobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (16% to 34% acetonitrile in 10 min, flow rate: 20 mL/min); Detector, UV 220&254 nm. This afforded (S)-cyclopropyl(5-(6-methoxypyridin-2-yloxy)-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.0033 g, 13%) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 0.79-0.87 (m, 1H), 0.91-1.00 (m, 2H), 1.10-1.18 (m, 4H), 1.39-1.49 (m, 1H), 1.79-1.84 (m, 2H), 1.97-2.09 (m, 3H), 2.18-2.41 (m, 2H), 2.62-2.79 (m, 3H), 3.12-3.19 (m, 2H), 3.62 (s, 3H), 4.15-4.27 (m, 1H), 4.72-4.89 (m, 1H), 6.41 (t, J=8.00 Hz, 2H), 7.36 (d, J=8.40 Hz, 1H), 7.55-7.65 (m, 2H), 7.79 (s, 1H), 7.96 (s, 1H). MS (ESI, pos. ion) m/z 488 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with brine (2×5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by preparative-HPLC with the following conditions (Waters I)
  7. custommobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (16% to 34% acetonitrile in 10 min, flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-8632a357a0d64acdb8b2781f86e7cad4
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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